DOCK2
Overview
DOCK2 (Dedicator of Cytokinesis 2) encodes a RAC1 guanine nucleotide exchange factor (GEF) that dimerizes with ELMO1 to activate RAC1 signaling. In cancer, DOCK2 mutations disrupt ELMO1/DOCK2/RAC1-mediated cytoskeletal remodeling, promoting invasive behavior.
Alterations observed in the corpus
- Significantly mutated in esophageal adenocarcinoma (EAC); two tumors carried two independent DOCK2 mutations each; ELMO1/DOCK2 pathway mutations increase NIH/3T3 cell invasion 2-7-fold in functional assays PMID:23525077
Cancer types (linked)
- Esophageal adenocarcinoma: significantly mutated gene; functional assays demonstrate pro-invasive activity PMID:23525077
Co-occurrence and mutual exclusivity
- DOCK2 mutations co-occur with ELMO1 mutations in EAC; both act upstream of RAC1 GTPase activation PMID:23525077
Therapeutic relevance
- No direct therapeutic data in the corpus; RAC1/ELMO1/DOCK2 axis is a candidate therapeutic target in invasive EAC.
Open questions
- Whether DOCK2 mutations drive invasion in vivo and whether DOCK2 loss-of-function or gain-of-function is the primary mechanism.
Sources
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